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马钱苷对脓毒症大鼠炎症反应及肠道屏障损伤的影响
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| 篇名： | 马钱苷对脓毒症大鼠炎症反应及肠道屏障损伤的影响 |
| TITLE： | Effects of loganin on inflammatory response and intestinal barrier damage in septic rats |
| 摘要： | 目的 探讨马钱苷通过调节Ras同源基因家族成员A（RhoA）/Rho相关卷曲螺旋形成蛋白激酶1（ROCK1）信号通路对脓毒症大鼠炎症反应及肠道屏障损伤的影响及机制。方法采用盲肠结扎和穿刺法建立脓毒症大鼠模型，并随机分为脓毒症组、马钱苷低剂量组（50mg/kg马钱苷，灌胃）、马钱苷高剂量组（200mg/kg马钱苷，灌胃）、阳性对照组（0.2mg/kg阿托伐他汀，腹腔注射）、马钱苷高剂量+溶血磷脂酸（LPA）组（200mg/kg马钱苷，灌胃+10mg/kgRhoA激活剂LPA，腹腔注射），另设假手术组，每组10只，每6h给药1次，连续给药4次。末次给药24h后，检测大鼠血清中炎症因子白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、IL-1β水平；观察大鼠回肠组织病理学变化并进行Chiu’s肠黏膜损伤评分；检测大鼠回肠组织中D-乳酸、D-氨基酸氧化酶（DAO）、内毒素水平，闭锁小带蛋白（ZO-1）、闭锁蛋白（Occludin）阳性染色面积百分比以及RhoA、ROCK1的蛋白相对表达水平。结果与脓毒症组比较，马钱苷低剂量组、马钱苷高剂量组大鼠的ZO-1、Occludin阳性染色面积百分比均显著升高，IL-6、TNF-α、IL-1β、DAO、D-乳酸、内毒素水平和Chiu’s肠黏膜损伤评分以及RhoA、ROCK1蛋白的相对表达水平均显著降低（P＜0.05），大鼠回肠组织的破坏程度得到缓解，组织水肿及炎性浸润均明显减轻，且马钱苷高剂量组的改善效果均优于马钱苷低剂量组（P＜0.05）；与马钱苷高剂量组比较，RhoA激活剂LPA可显著逆转上述指标的变化趋势（P＜0.05）。结论马钱苷能减轻脓毒症大鼠炎症反应及肠道屏障损伤，其机制与抑制RhoA/ROCK1信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of loganin on inflammatory response and intestinal barrier damage in septic rats by regulating the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase 1 （ROCK1） signaling pathway. METHODS A sepsis rat model was established by cecal ligation and puncture， and randomly divided into sepsis group， loganin low-dose group （50 mg/kg loganin， gavage）， loganin high-dose group （200 mg/kg loganin， gavage）， positive control group （0.2 mg/kg atorvastatin， intraperitoneal injection）， and loganin high-dose + lysophosphatidic acid （LPA） group （200 mg/kg loganin gavage and intraperitoneal injection of 10 mg/kg RohA activator LPA）. An additional sham surgery group was established. Each group consisted of 10 rats， and medications were administered once every 6 hours for 4 times. After 24 hours of the last intervention， the levels of serum inflammatory factors interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β were detected. The pathological changes of ileal tissue were observed and Chiu’s intestinal mucosal injury score was also performed. The levels of intestinal function-lactate dehydrogenase （D-lactate）， D-amino acid oxidase （DAO） and endotoxin， the percentages of zonula occludens-1 protein （ZO-1） and Occludin positive staining area， as well as protein expressions of RhoA， and ROCK1 were all detected. com RESULTS Compared with the sepsis group， the percentages of ZO-1 and Occludin positive areas increased significantly in loganin low-dose and high-dose groups； while the levels of IL-6， TNF-α， IL-1β， DAO， D-lactate and endotoxin， Chiu’s intestinal mucosal injury score as well as protein expressions of RhoA and ROCK1 decreased significantly （P＜0.05）； the destruction of rat ileal tissue was alleviated， and tissue edema and inflammatory infiltration were significantly reduced； moreover， the improvement effect in loganin high-dose group was superior to that in loganin low-dose group （P＜0.05）. Compared with loganin high-dose group， RhoA activator LPA reversed the trend of changes in the above indicators （P＜0.05）. CONCLUSIONS Loganin can alleviate inflammatory response and intestinal barrier damage in septic rats， the mechanism of which may be associated with inhibiting RhoA/ROCK1 signaling pathway. |
| 期刊： | 2025年第36卷第05期 |
| 作者： | 王灿；李岩涛；周正；王璐鹏；高媛媛；范少希 |
| AUTHORS： | WANG Can，LI Yantao，ZHOU Zheng，WANG Lupeng，GAO Yuanyuan，FAN Shaoxi |
| 关键字： | 马钱苷；脓毒症；RhoA/ROCK1信号通路；炎症反应；肠道屏障损伤 |
| KEYWORDS： | loganin； sepsis； RhoA/ROCK1 signaling pathway； inflammatory response； intestinal barrier damage |
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